Controlled release systems for drugs have received increased attention and application over the past decade, as they frequently provide a dosing regimen significantly superior to conventional techniques. By allowing a near constant level of drug to be maintained within the patient, treatment efficacy can be greatly improved. In the formulation of controlled release therapeutics, it is frequently desirable to disperse the material into very fine, uniform particles. With proteinaceous therapeutics, the generation of such fine particles is particularly problematic. Existing practices have difficulty achieving the desired particle size distribution, expose the protein to denaturing conditions such as heat or air, or leave residual product contamination, which necessitates fewer processing. The specific aim of the present proposal is to develop a protein comminution process that avoids the aforementioned difficulties. The proposed process uses nontoxic liquefied gases, compressed gases, or critical fluids (which have properties intermediate to gases and liquids) to form small (l-5 mu m), monodisperse protein particles 'without first dissolving the material in a liquid solvent. The product material is expected to retain full activity and be devoid of residual processing chemicals such as solvents, salts, or surfactants. PROPOSED COMMERCIAL APPLICATIONS: The proposed process can benefit the pharmaceutical and biotech industries by yielding improved efficacy of therapeutic products with less residual contamination, The technique can be useful in obtaining a desired particle size in drug manufacture, and may also prove useful in terms of controlled release formulations such as microspheres or aerosol delivery systems.